tbuckley/cabot-search huggingface dataset:
Risk reduction of CNS relapse in diffuse large B cell lymphoma with intrathecal methotrexate prophylaxis: A single institution retrospective study.
Authors: Christopher Hino, Curtis Lacy, Joel M. Brothers, Huynh Le Cao, Hamid R. Mirshahidi, Kiwon Park, Mojtaba Akhtari
Journal: Journal of Clinical Oncology (2023)

e19531 Background: Central nervous system (CNS) relapse is an infrequent but serious and challenging complication in diffuse large B-cell lymphoma (DLBCL) that carries a dismal prognosis. While several risk factors have been identified to stratify the risk for CNS relapse including the 2015 CNS internal Prognostic index (CNS-IPI), controversy still remains regarding the indication, timing, and method of CNS prophylaxis. The purpose of this study was to determine whether IT-MTX reduced the risk of CNS relapse, as well as treatment related and financial toxicity of CNS prophylaxis. Methods: We performed a single-center, retrospective analysis on a cohort of 192 patients with DLBCL who had received treatment between January 2010- August 2022. Patients were identified by using ICD10 code diagnosis in the electronic medical records system. We included patients of all stages of disease and CNS-IPI scores along with patients with testis, breast, sinus, and bone marrow extranodal involvement. Patients with primary CNS disease and primary mediastinal disease were excluded from the study. Clinical data collected by chart review included age at time of diagnosis, sex, performance status, LDH level, disease stage, number and type of therapies administered including IT-MTX, extranodal involvement, MYC/BCL2/BCL6 translocation status, HIV status, cell of origin (COO), treatment response. Toxicities and complications thought to be associated with IT-MTX prophylaxis were also documented in addition to total costs of treatment for each patient. Patient characteristics were compared using Fisher exact test or Pearson’s chi-square test. Results: In patients with intermediate to high CNS relapse risk (CNS-IPI 2-5) IT-MTX did not reduce the 1 year risk of CNS relapse (RR 1.1296, 95% CI 0.1933 to 6.6012, P = 0.08924). The median time to CNS relapse was longer in patients who had received IT-MTX (13.5 months) vs those who did not (7 months). Thirty eight (52.8%) patients reported adverse side effects of any kind as a result of IT-MTX administration, with 23.6% of patients developing grade 2-3 adverse events. The average cost for CNS-prophylaxis was estimated to be approximately $8,059.04 over a patient’s treatment course, but as high as $20,140. Conclusions: In conclusion, our study highlights the necessity to develop improved standardized guidelines for use of CNS prophylaxis in patients with DLBCL. The results from our retrospective study add to the growing body of literature showing IT-MTX has limited and potentially transient effectiveness in preventing CNS relapse. Given the high rate of side effects and significant cost of IT-MTX, we recommend that clinicians carefully consider the risks and benefits of prophylaxis before prescribing IT-MTX for CNS-prophylaxis.
Comparative efficacy of later-line therapies for metastatic colorectal cancer (mCRC) using novel methods for patient survival data reconstruction and network meta-analysis (NMA) of survival curves.
Authors: Ivo Abraham, Mavis Obeng-Kusi, Denise Roe, Brian L Erstad
Journal: Journal of Clinical Oncology (2023)

e15611 Background: NMAs of cancer treatments are usually based on the proportional hazard assumption (PHA) which implies a constant hazard ratio as well as treatment effect on only scale parameter and therefore not reflecting clinical dynamics of survival outcomes over time. Multivariate NMA which does not rely on the PHA is often constrained by lack of individual patient-level data (IPD). We applied a novel method of reconstructing pseudo-IPD from published survival curves that enabled application of a dynamic method of NMA of survival curves without PHA constraint to compare the efficacy of 6 later-line therapies for metastatic colorectal cancer (mCRC), compared to placebo. Methods: We identified 8 phase II/III trials reporting the efficacy of 6 later-line therapies for mCRC from PubMed, Embase, Scopus and Cochrane Library. Trial survival curves were reconstructed based on pseudo-IPD generated using the Guyot method, and the estimated survival proportions and hazard ratios (HRs) over 12 months (12m) of follow up were calculated using a random effects lognormal distribution model with placebo as the common comparator. Results: Compared to placebo, 12m PFS HRs varied from 0.29 (95%CrI = 0.19-0.44) for TAS+bevacizumab to 0.72 (95%CrI = 0.62-0.85) for atezolizumab. Similarly, OS HRs ranged from 0.55 (95%CrI = 0.26-0.92) for TAS+bevacizumab to 1.01 (95%CrI = 0.79-1.20) for atezolizumab (Table). Conclusions: In this NMA of survival curves, all therapies except atezolizumab were superior to placebo in PFS and OS over 12m follow up period. TAS+bevacizumab provided the highest survival advantage over placebo, with fruquintinib, regorafenib, and TAS-102 also showing survival benefits. TAS+bevacizumab may be the preferred choice for later-line mCRC treatment. [Table: see text]
Multi-cancer early detection screening tools: A dream come true or a nightmare in the offing.
Authors: Leonard M Fleck, Aakash Dave
Journal: Journal of Clinical Oncology (2023)

e18926 Background: US cancer deaths were at 610,000 in 2022 with 1.9 million new diagnoses of cancer, 86% of which were patients over age fifty. Roughly 150,000 advanced cancers were diagnosed with five current screening techniques. That leaves 1.75 million cancers to be diagnosed symptomatically, largely in advanced stages. The dream is to screen in a minimally invasive fashion for multiple types of cancer at earlier, treatable, life-saving stages. The Galleri test claims to fulfill that dream by identifying more than fifty different cancers, and their location, using a blood test that captures ctDNA linked to aberrant methylation. As their dream approaches reality, with a dozen US hospital systems already offering Galleri, a fiscal and ethical nightmare is likely to ensue. We will demonstrate to providers that Galleri’s analytical validity and clinical utility is marginal at best – largely due to uncertainty surrounding the nature of those fifty malignancies. Methods: Systematic review of literature was performed across multiple databases using the key terms "Cancer Early Detection" AND OR "MCED" AND OR "GALLERI." Grail’s optimistic portrayal of the test’s current efficacy is largely derived from Hubbell and colleagues’ recent work modelling a Galleri-like test that claimed an achievable 24% reduction in cancer mortality (~150,000 lives). Critics contend that their assumptions are too optimistic. The natural histories of most of those fifty cancers are poorly understood, such as tumor latency periods, which means the cancer shift detection to an earlier stage is unknowable. Moreover, we cannot know whether these cancers would have been caught earlier, symptomatically, and successfully treated - which is true of 68% of diagnosed cancers. Etzioni and colleagues concluded that 6% of cancer deaths might be reduced by Galleri, despite that number is still uncertain and optimistic. Galleri cannot take credit for those saved lives. Results: GRAIL proposes population-based screening for 110 million Americans over age fifty annually at a cost of $950 per test. That would add over $100 billion per year to the health costs to discover no cancer in 99% of the persons tested. Roughly $50 billion would be added to Medicare program costs, now at $1 trillion. To save 18,000 Medicare lives would cost $2.8 million per life saved, a significant misallocation of Medicare resources, given many less costly opportunities to save more lives. Finally, individuals with marginal or no health insurance would be informed by Galleri they had an early-stage cancer unaffordable to treat. They represent statistically salvageable lives not actually salvaged, which is a presumptive injustice. This argument holds, despite the company’s pledge to reduce cost by over 40% over four years. Conclusions: In sum, Galleri, as a population-based cancer screening test, is not economically affordable, not ethically equitable, and only marginally medically beneficial.
Real-world experience with atezolizumab plus bevacizumab in the management of non-resectable hepatocellular carcinoma refractory to first-line systemic therapy: Review of literature.
Authors: Vishal Devarkonda, Laxman Yashwant Byreddi, Shravya Balmuri, Thulasi Gudi, Shiva Jashwanth Gaddam, Dinesh Keerty
Journal: Journal of Clinical Oncology (2023)

e16189 Background: Hepatocellular carcinoma is the fifth most common cancer worldwide and the third leading cause of cancer-associated deaths. In 2020, the positive results of the IMbrave 150 trial and FDA (Food and Drug Administration) approval subsequently revolutionized the management of non-resectable hepatocellular carcinoma as the first-line treatment. However, their role as second-line therapy in people refractory to systemic therapy needs to be better studied. We perform a comprehensive literature review evaluating outcomes of atezolizumab plus bevacizumab in patients refractory to first-line systemic therapy. Methods: We performed a comprehensive literature search of PubMed, Embase, and Cochrane, evaluating the outcomes of atezolizumab plus bevacizumab in patients refractory to first-line systemic therapy. Results: Conclusions: Atezolizumab plus Bevacizumab is Safe and effective in the patient’s refractory to prior systemic therapy. However, when used as a second-line therapy, patients tend to have lower Median Odds of survival and Median progression-free survival. The outcome also changes with the type of prior systemic chemotherapy, with initial hyper-progression reported with prior therapy with lenvatinib. The AFP response at six weeks could be a predictive indicator of disease progression. [Table: see text]
Bone metastasis in patients with germ-cell tumors: Analysis of survival outcomes and prognostic factors.
Authors: Rebecca Hassoun, Jennifer King, Sandra K. Althouse, Nasser H. Hanna, Lawrence H. Einhorn, Nabil Adra
Journal: Journal of Clinical Oncology (2023)

e17029 Background: Bone metastasis (BM) is uncommon in patients with germ-cell tumor (GCT). There is lack of data regarding optimal treatment approach. We report the outcomes and prognostic factors in 99 pts with BM treated at our institution. Methods: We identified 99 pts with GCT and BM treated at Indiana University between year 1986-2021. Kaplan-Meier methods were used for progression free survival (PFS) and overall survival (OS) analysis. Results: Median age was 31.5 (range, 13.1-58.8). Primary tumor histology was non-seminoma in 77 and pure seminoma in 22. Predominant histology was seminoma in 26, yolk sac tumor 23, mixed 16, embryonal ca 12, teratoma 10, choriocarcinoma 9. Other mets sites included lungs in 68, RP LNs in 63, liver in 34, brain in 19. BM location was spine in 73, pelvic bones in 22, humerus/femur in 14, ribs in 10, sternum/clavicle in 7. Median pre-chemo AFP was 438 (range, 1-75,414) and hCG 80 (range, 0.7-1,700,000). 1L chemo was BEP x4 in 46, VIPx4 in 10, BEP x3 + EP x1 in 8, EP x4 in 8, BEP x3 in 7, VIPx3 in 1, and other in 19. Histology of BM resection for those who underwent surgery was viable non-teratoma GCT in 6, teratoma in 1, malignant transformation of teratoma in 3, and necrosis in 3. 28 had radiotherapy to symptomatic BM. 80 (82.5%) pts progressed after 1L chemo and 46 (53.5%) progressed after 2L chemo. With median f/u from diagnosis of 5.7 years, 5 yr PFS was 17.8% (95% CI 10.3-27.0) and 5 yr OS was 59.9% (95% CI 47.9-70.0). For pts with pure seminoma, 5 yr PFS was 29.8% (95% CI 12.4-49.5) and 5 yr OS 83.1% (95% CI 55.7-94.3). For non-seminoma: 5 yr PFS was 14.6% (95% CI 6.9-25.1) and 5 yr OS 52.2% (95% CI 38.4-64.2). Multivariable analysis indicated that pts with concurrent liver and/or brain mets had worse OS. Conclusions: Outcomes of pts with GCT and BM are inferior than what is expected based on IGCCCG risk categories. Pts with concurrent liver and/or brain mets have particularly worse OS outcomes. [Table: see text]
APPROACH trial: Multimodal approach in patients with mHSPC: A pragmatic, randomized, phase 3 trial of androgen-deprivation therapy (ADT) plus apalutamide (APA) versus ADT plus apalutamide (APA) and local treatment—Meet-URO 29 study.
Authors: Valentina Guadalupi, Alessandro Rametta, Elena Verzoni, Melanie Claps, Pierangela Sepe, Marco Stellato, Achille Bottiglieri, Mario Catanzaro, Barbara Avuzzi, Maria Chiara Sighinolfi, Bernardo Rocco, Barbara Jereczek, Massimo Di Maio, Nicola Nicolai, Filippo G. De Braud, Giuseppe Procopio
Journal: Journal of Clinical Oncology (2023)

TPS5115 Background: it is reasonable to offer radiotherapy (RT) to improve outcomes for patients with newly diagnosed M1 prostate cancer with &lt; 5 bone metastases (HORRAD) or low volume disease (STAMPEDE) (Burdett, S et al., Eur. Urol. 2019). Data from clinical randomized trials evaluating feasibility and overall benefit of cytoreductive radical prostatectomy (cRP) in oligometastatic ormone sensitive patients are not available. The rationale for performing cytoreductive radical prostatectomy is to eliminate lethal clones ofcastration-resistant intraprostatic PCa, which can favor the process of metastasis (A Heidenreich et al. Current Opinion in Urology 2020), in order to improve OS and PFS and to prevent local progression and correlated events. Methods: APPROACH is an Italian multicenter study, which is enrolling ~566 pts with oligometastatic hormone sensitive prostate cancer who are candidates to receive treatment with apalutamide. After 6 months from the start of treatment, patients will be randomized 1:1 to receive local treatment or not in addition to apalutamide (investigator's choice between primary radiotherapy and cytoreductive prostatectomy). Primary end point: To determine whether treatment with apalutamide plus ADT for 6 months followed by locoregional treatment with radiotherapy or radical prostatectomy has better efficacy than treatment with apalutamide plus ADT alone in terms of radiographic progression-free survival (rPFS). Secondary end points: To evaluate tumor shrinkage after locoregional approach and to evaluate short and long-term side effects after locoregional surgery or RT, time to PSA progression, time to castration resistance, cancer specific survival, overall survival and quality of life according to EPIC-26 and EQ-5D-5L questionnaires. Clinical trial information: NCT05649943 .
CarePoint assay in the management of bladder cancer: A pilot study.
Authors: Sam S. Chang, Jennifer Linehan, Kristen R. Scarpato, Jeffrey C. Bassett, Rodney Brenneman
Journal: Journal of Clinical Oncology (2023)

e16593 Background: Bladder cancer afflicts over 700,000 patients in the US and is one of the most expensive cancers to treat. Given a recurrence rate of up to 70%, regular often prolonged surveillance is required. In addition to urine based tests, current standard evaluation includes cystoscopy which is burdensome for patients and physicians; there has long been a need for a reliable non-invasive alternative diagnostic tool. While there is a wealth of literature on urinary biomarkers, no single biomarker has demonstrated consistent high sensitivity and specificity. Methods: The CarePoint Assay, a point-of-care (POC) tool, can perform multiple biomarker tests simultaneously. In this study, urine was collected from patients undergoing urologic evaluation for hematuria from three separate institutions. The urine was sent for central evaluation and the CarePoint Assay was used to detect the bladder cancer biomarker BTA. POC results were then compared to results from a highly sensitive 6-hour ELISA. The accuracy of distinguishing high-grade tumors, low-grade tumors and no tumor present were compared between the two methods. Results: The CarePoint Assay demonstrated excellent correlation with the ELISA in detecting biomarker levels and distinguishing high-grade tumors as well as a superior specificity (88% versus 77%) for ELISA, sensitivity (52% vs. 72%) for ELISA and a limit of detection of 2.55 ng/mL (16 picomolar). Conclusions: With this high performance, the CarePoint Assay has the ability to detect and multiplex multiple other bladder cancer biomarkers with higher sensitivity and specificity. Additional biomarker analysis using the CarePoint Assay may yield the medically desired higher levels of sensitivity and specificity for a non-invasive point-of-care bladder cancer test, ultimately limiting the patient burden of bladder cancer surveillance.
Impact of EBV positivity on clinical outcomes in nasopharyngeal cancer.
Authors: Bipin Ghimire, Ujjwal Karki, Emma Herrman, Shrinjaya Thapa, Shiva Shrotriya, Shyam K. Poudel, Nwabundo Ifeyinwa Anusim, Daniel Ezekwudo, Ishmael A. Jaiyesimi
Journal: Journal of Clinical Oncology (2023)

e18021 Background: Nasopharyngeal carcinoma (NPC) is a rare malignancy with unique geographical distribution. Epstein Barr virus (EBV) plays a key role in the pathogenesis of NPC, with pre and post-treatment serum EBV DNA level as an established prognostic indicator. However, evidence regarding the impact of the tumor cells’ EBV positivity on clinical outcomes is inconsistent. Methods: After IRB approval, we performed a retrospective chart review on NPC patients aged above 18 years seen at Corewell Health William Beaumont University Hospital between July 2015 and December 2020. The Epstein Barr encoding region in-situ hybridization from the biopsy sample determined EBV positivity. We compared progression-free survival (PFS) and overall survival (OS) based on EBV positivity status. Results: A total of 60 NPC patients were included: 19 were EBV-positive, 20 were EBV-negative, and 21 were EBV-unknown. The median age at diagnosis was 50.7 years, and 58.3 years in EBV-positive and negative groups respectively. Most patients in both groups were male (68.4% vs 65%) and had advanced (stage III or stage IV) disease (84.2% vs 75%). The median follow-up duration was 37.3 months. Median PFS and OS were 41 months and 114 months respectively in EBV-negative patients, while median PFS and OS were not reached in EBV-positive patients. There was no significant difference in PFS (0.944) and OS (0.117) among the EBV-positive and negative groups. Among advanced-stage patients, the median PFS was 33 months and 31 months in EBV-negative and EBV-positive groups, respectively, while median OS was not reached in both groups; the difference in PFS (p = 0.821) and OS (0.240) was statistically non-significant. When compared among patients with EBV-positive, negative, and unknown status, PFS was statistically non-significant (p = 0.347) but there was a statistical difference in OS (0.027). Conclusions: Our analysis suggests that the EBV status of the tumor cells does not predict clinical outcomes (PFS or OS) in NPC patients. Even though the OS trend favored EBV-positive patients overall and among those with advanced disease, it was not statistically significant. A difference in OS was seen when patients with unknown status were included and analyzed together with EBV-positive and negative patients, which raises the question of whether the outcome would be different if the majority of patients with unknown status belonged to either the EBV-positive or negative group. With studies in the literature reporting disparate findings, larger prospective studies are needed to better illustrate the impact of tumor cells' EBV positivity on clinical outcomes in NPC.
Phase II trial of terelizumab combined with radiotherapy of locally advanced unresectable esophageal squamous cell carcinoma: TREC trial.
Authors: Changmin Liu, Zeshun Yu, Yanzhang Hao, Feng Wang, Zhenbo Wang, Lijun Tian, Yue Wang, Fangling Ning
Journal: Journal of Clinical Oncology (2023)

e16086 Background: Concurrent chemoradiotherapy (CCRT) is the standard therapy for locally advanced unresectable esophageal squamous cell cancer (ESCC)，However, some patients cannot tolerate or are unwilling to CCRT. The aim of this phase II trial was to assess the efficacy and safety of the tirelizumab combined with radiotherapy in patients of locally advanced unresectable ESCC. Methods: Key eligibility criteria were as follows: ESCC of clinical stage Ⅱ-Ⅳa; aged 18 to 90 years; cannot tolerate or are unwilling to CCRT; ECOG performance status 0 or 1; and performed radiotherapy: Involvement field irradiation, nodal GTV (GTVn) (regional lymphatic metastasis) radiotherapy dose 60Gy, the esophageal gross tumor volume (GTVt) radiotherapy dose 50Gy, if the gastroscope pathology is completely relieved, otherwise it is 60Gy. All patients registered before radiotherapy. The patient received concurrent therapy with tirelizumab (200mg every time, 3-week cycle), until the disease progresses or clinical benefits are lost (the longest time is 12 months). The primary endpoint was the esophageal gross tumor pathological complete remission rate (pCR). Results: Between 01 August 2021 and 31 December 2022, 31 patients were enrolled, and 27 completed radiotherapy and at least two times of tirelizumab treatment. Data cutoff date was 31 January 2023, median follow-up time among survivors after radiotherapy was 9 months (range 4-20). The esophageal gross tumor pCR rate was 66.7% (95% CI, 14.3%-52.3%) and treatment-related adverse events (TRAEs) of low severity (grade 1-2, 48.1%; grade 3, 7.4%; grade 4-5, no). No treatment-related mortality occurred. Two (7.4%) patients had tumor recurrence and two (7.4%) patients died (Infection and heart disease). The 1-year PFS rate, median PFS and median OS had not been reached yet. For locally advanced unresectable ESCC that can't receive CCRT, the combination of tirelizumab and radiotherapy shows promising efficacy and acceptable toxicity, providing a feasible and effective choice. The research of long-term survival analysis is under way. Conclusions: Concurrent radiotherapy with tirelizumab shows promising efficacy and controllable safety for patients with locally advanced ESCC who are unable or unwilling to undergo CCRT, and warrants further evaluation in larger studies. Clinical trial information: ChiCTR2100053182 .